Regulation of genes via application of specific and selective electrical and electromagnetic signals

Abstract

Methods and devices for the regulation of gene expression by cells via the application of fields generated by specific and selective electric and electromagnetic signals so as to target diseased or injured tissue for treatment. By gene expression is meant the up regulation or down regulation of the process whereby specific portions (genes) of the human genome (DNA) are transcribed into mRNA and subsequently translated into protein. Methods and devices are provided for the targeted treatment of injured or diseased tissue that include providing specific and selective electric and electromagnetic signals and exposing tissue to the fields generated by the signals so as to regulate gene expression. In particular, methods and devices are provided for the targeted treatment of bone defects, osteoarthritis, osteoporosis, cancer, and other disease states.

1 . A method of treating injured or diseased tissue, comprising the steps of:
 generating a signal that when applied to a field generating device operatively disposed with respect to the injured or diseased tissue causes the generation of an electric field having an amplitude of about 2-40 mV/cm in the injured or diseased tissue that is specific and selective for substantially up-regulating or down-regulating the gene expression of at least one target gene of the injured or diseased tissue when said electric field is applied to the injured or diseased tissue containing said at least one target gene; and   exposing the injured or diseased tissue to the specific and selective electric field generated by said field generating device upon the application of said signal thereto for a predetermined duration of time per 24 hour period at a predetermined duty cycle selected so as to optimize the selective regulation of expression of said at least one target gene in said injured or diseased tissue.   
     
     
         2 . The method of  claim 1  wherein the specific and selective electric field selectively varies the gene expression of first and second target genes of the injured or diseased tissue and said exposing step further comprises the step of selectively up-regulating expression of the first target gene and/or down-regulating expression of the second target gene. 
     
     
         3 . The method of  claim 1  wherein the exposing step comprises the step of exposing an articular chondrocyte to the specific and selective electric field so as to up-regulate expression of at least one target gene encoding tissue inhibitors of metalloproteinase. 
     
     
         4 . The method of  claim 1  wherein the exposing step comprises the step of exposing cancerous tissue to the specific and selective electric field so as to up-regulate expression of at least one gene encoding tissue inhibitors of metalloproteinase. 
     
     
         5 . The method of  claim 1  wherein the generating step comprises the step of selectively varying the amplitude, duration, duty cycle, frequency, and/or waveform of the signal until the desired expression of said at least one target gene in the injured or diseased tissue in response to the specific and selective electric field resulting from application of the signal to said field generating device is substantially optimized. 
     
     
         6 . The method of  claim 1  further comprising the step of providing the signal from a remote source. 
     
     
         7 . The method of  claim 1  wherein the specific and selective electric field is applied to said injured or diseased tissue as a direct current, as a combined field, via capacitive coupling, or inductive coupling. 
     
     
         8 . A method for treating cancerous tissue comprising the steps of:
 generating at least one first electric field by applying a signal to a field generating device operatively disposed with respect to the cancerous tissue so as to cause the generation of said first electric field at an amplitude of about 2-40 mV/cm in the cancerous tissue that is specific and selective for varying the gene expression of at least one gene in the cancerous tissue encoding metalloproteinase or tissue inhibitors of metalloproteinase when said at least one first electric field is applied to the cancerous tissue containing said at least one gene; and   exposing the cancerous tissue to the first electric field for a predetermined duration of time per 24 hour period at a predetermined duty cycle selected so as to optimize the (a) selective down-regulation of the expression of the gene encoding metalloproteinase and/or (b) selective up-regulation of the expression of the gene encoding tissue inhibitors of metalloproteinase.   
     
     
         9 . The method of  claim 8  wherein the first electric field is applied to said cancerous tissue as a direct current, as a combined field, via capacitive coupling, or inductive coupling.